Phosphatidylcholine-specific phospholipase c from Listeria monocytogenes is an important virulence factor in murine cerebral listeriosis

Meningoencephalitis is a serious and often fatal complication of Listeria m onocytogenes infection. The aim of the present study was to analyze the rol e of internalin A (InlA) and B, which are involved in the invasion of L. mo nocytogenes into cultivated host tissue cells, and that of phosphatidylchol ine-specific phospholipase C (PlcB), which mainly promotes the direct cell- to-cell spread of L. monocytogenes, in murine cerebral listeriosis by use o f an InlA/B (Delta inlAB2)- and a PlcB (Delta plcB2)-deficient isogenic del etion mutant strain and the wild-type (WT) L. monocytogenes EGD. Listeria s trains were directly applied to the brain, a technique which has been emplo yed previously to study the pathogenesis of cerebral listeriosis (D. Schlut er, S. B. Oprisiu, S. Chahoud, D. Weiner, O. D. Wiestler, H. Hof, and M. De ckert-Schluter, fur. J. Immunol. 25:2384-2391, 1995). We demonstrated that PlcB, but not InlA or InlB, is an important virulence factor in cerebral li steriosis. Nonimmunized mice infected intracerebrally with the Delta plcB2 strain survived significantly longer and had a reduced intracerebral bacter ial load compared to mice infected with the Delta inlAB2 strain or WT bacte ria. In addition, immunization with the WT prior to intracerebral infection significantly increased the survival rate of mice challenged intracerebral ly with the Delta plcB2 strain compared to that of mice infected with the W T or Delta inlAB2 strain. Histopathology revealed that the major difference between the various experimental groups was a significantly delayed intrac erebral spread of the Delta plcB2 mutant strain, indicating that cell-to-ce ll spread is an important pathogenic feature of cerebral listeriosis. Inter estingly, irrespective of the Listeria mutant used, the apoptosis of hippoc ampal and cerebellar neurons and an internal hydrocephalus developed in sur viving mice, indicating that these complications are not dependent on the v irulence factors InlA/B and PlcB. In conclusion, this study points to PlcB as a virulence factor important for the intracerebral pathogenesis of murin e L. monocytogenes meningoencephalitis.